Oxygen (O-2) generating biomaterials are emerging as important compositions to improve our capabilities in supporting tissue engineering and regenerative therapeutics. Several in vitro studies demonstrated the usefulness of O-2 releasing biomaterials in enhancing cell survival and differentiation. However, more efforts are needed to develop materials that can provide sustained O-2 release for the long-term. In this paper, we present different O-2 generating sources, including hydrogen peroxide, sodium percarbonate, calcium peroxide and magnesium peroxide, and also cover types of carriers and relevant methods of fabricating O-2 generating systems. Then, the applications of O-2 generating materials in supporting engineered constructs, supplying high O-2 demanding cell transplants, and supporting ischemic tissues are discussed. Moreover, the challenges and future perspectives are highlighted.